{
  "abstract": "Introduction Some intensive care unit (ICU) patients develop an extremely deep and sustained immunosuppression that increases the risk of secondary infections and can ultimately compromise survival. Thanks to an easily accessible and simplified immune monitoring to identify immunological failure, a personalised immune restoration approach is now feasible. Among the different therapeutic strategies in this field, interferon gamma (IFN-γ) is probably the most interesting drug to reduce the burden of secondary infections in the ICU.Methods and analysis This is a two parallel group multicentre blinded add-on randomised trial comparing immunorestoration by subcutaneous injection of IFN-γ to standard of care in targeted ICU patients. The study will be performed in 23 ICUs in France. Patients hospitalised in the ICU for a week, with multiple organ failure defined by a sequential organ failure assessment score ≥6 during this first week, will be enrolled. If within 96 hours after inclusion, these patients express immunosuppressed features defined by a low absolute lymphocyte count (<1000/×10 9/L) and low expression of human leucocyte antigen-DR (HLA-DR) on monocytes (<8000 antibodies bound per cell [Ab/c]) they will be randomised (1:1) to receive either five subcutaneous injections of IFN-γ or placebo in addition to standard of care. The primary outcome will be the incidence of secondary infection episodes at day 90 validated by an independent adjudication committee based on the current definitions (Centers for Disease Control and Prevention surveillance definitions). Secondary outcomes will be all-cause ICU mortality at day 90, length of stay in the ICU and in the hospital at day 90, antibiotic and antifungal consumption at day 90, percentage of biological immune restoration (defined as a monocytic HLA-DR >13 500 antibodies bound per cell and an absolute lymphocyte count >1200 ×109/L) at day 10, healthcare costs at day 90 and rate of serious adverse reactions and suspected unexpected serious adverse reaction at day 90. We plan to randomise 326 patients.Ethics and dissemination The study will be implemented in accordance with European regulations and was independently reviewed and approved by the French Ethics Committee Comité de Protection des Personnes Ile de France III (EUCT number: 2024-516780-93-00). The results will be reported in international peer-reviewed journals and presented at international and national conferences.Trial registration number NCT06774235.",
  "authors": [
    {
      "affiliations": [
        "Inserm CIC 1435, Centre Hospitalier Universitaire de Limoges, Limoges, Aquitaine-Limousin-Poitou-Charentes, France",
        "Réanimation polyvalente, Centre Hospitalier Universitaire de Limoges, Limoges, Aquitaine-Limousin-Poitou-Charentes, France",
        "UMR Inserm 1092, Université de Limoges, Limoges, Aquitaine-Limousin-Poitou-Charentes, France"
      ],
      "name": "Ana C Hernandez Padilla"
    },
    {
      "affiliations": [
        "Inserm CIC 1435, Centre Hospitalier Universitaire de Limoges, Limoges, Aquitaine-Limousin-Poitou-Charentes, France",
        "Réanimation polyvalente, Centre Hospitalier Universitaire de Limoges, Limoges, Aquitaine-Limousin-Poitou-Charentes, France",
        "UMR Inserm 1092, Université de Limoges, Limoges, Aquitaine-Limousin-Poitou-Charentes, France"
      ],
      "name": "Thomas Daix"
    },
    {
      "affiliations": [
        "University of Washington School of Medicine, Seattle, Washington, USA"
      ],
      "name": "Richard S Hotchkiss"
    },
    {
      "affiliations": [
        "Laboratoire d’Immunologie, Hôpital Edouard Herriot, Centre Hospitalier Universitaire de Lyon, Lyon, France"
      ],
      "name": "G Monneret"
    },
    {
      "affiliations": [
        "Médecine Intensive Réanimation, CHU de Rennes, Rennes, Brittany, France",
        "MOBIDIC - UMR Inserm U1236, Université de Rennes 1, Rennes, Brittany, France"
      ],
      "name": "Jean Marc Tadie"
    },
    {
      "affiliations": [
        "Laboratoire d’hématologie biologique, Centre Hospitalier Universitaire de Limoges, Limoges, Aquitaine-Limousin-Poitou-Charentes, France"
      ],
      "name": "Robin Jeannet"
    },
    {
      "affiliations": [
        "Inserm CIC 1435, Centre Hospitalier Universitaire de Limoges, Limoges, Aquitaine-Limousin-Poitou-Charentes, France",
        "Réanimation polyvalente, Centre Hospitalier Universitaire de Limoges, Limoges, Aquitaine-Limousin-Poitou-Charentes, France"
      ],
      "name": "Olivier Plateker"
    },
    {
      "affiliations": [
        "Inserm CIC 1435, Centre Hospitalier Universitaire de Limoges, Limoges, Aquitaine-Limousin-Poitou-Charentes, France",
        "Réanimation polyvalente, Centre Hospitalier Universitaire de Limoges, Limoges, Aquitaine-Limousin-Poitou-Charentes, France"
      ],
      "name": "Julien Vaidie"
    },
    {
      "affiliations": [
        "Université Paris-Est Créteil Val de Marne, Créteil, Île-de-France, France",
        "URCEco, Assistance Publique - Hopitaux de Paris, Paris, France",
        "Hôpital Hôtel-Dieu de Paris, Paris, Île-de-France, France"
      ],
      "name": "Isabelle Durand-Zaleski"
    },
    {
      "affiliations": [
        "Centre of Clinical and Research Data, Centre Hospitalier Universitaire de Limoges, Limoges, France",
        "Inserm U1094, IRD UMR270, Université de Limoges, Limoges, Aquitaine-Limousin-Poitou-Charentes, France"
      ],
      "name": "Julien Magne"
    },
    {
      "affiliations": [
        "Inserm CIC 1415, CHRU de Tours, Tours, Centre-Val de Loire, France",
        "Inserm SPHERE U1246, Université de Tours, Tours, Centre-Val de Loire, France"
      ],
      "name": "Bruno Giraudeau"
    },
    {
      "affiliations": [
        "Inserm CIC 1435, Centre Hospitalier Universitaire de Limoges, Limoges, Aquitaine-Limousin-Poitou-Charentes, France",
        "Réanimation polyvalente, Centre Hospitalier Universitaire de Limoges, Limoges, Aquitaine-Limousin-Poitou-Charentes, France",
        "UMR Inserm 1092, Université de Limoges, Limoges, Aquitaine-Limousin-Poitou-Charentes, France"
      ],
      "name": "Bruno François"
    }
  ],
  "title": "Prevention of secondary infections by interferon-gamma in ICU-acquired sustained immune suppression in France: study protocol of the PLATINIUM randomised trial",
  "uid": "770387a5-70c3-5ec0-a3c4-982bd8ab92f8"
}